The long-term objective of this research is to define the role of FGF-10 in ovarian function. This factor is essential for epithelial-stromal cell interactions in other organs, and is present in the neonatal and adult ovary. This proposal will investigate the hypothesis that FGF-10 plays a major role in folliculogenesis, and is necessary for normal ovarian function and female fertility. Preliminary studies indicate that FGF-10 -/- deficiency blocks follicle development prior to antrum formation, and suggest aberrant luteinization and ovarian hormone production. The proposed experiments will specifically identify the role of FGF-10 in these processes. The specific aims are (1) to determine whether FGF-10 deficiency affects folliculogenesis, response to gonadotropins, hormone production, and/or ovulation in vivo, (2) to investigate whether FGF-10 deficiency affects expression of genes encoding markers of folliculogenesis, and (3) to compare follicle development in FGF-10 -/- vs. FGF-10 +/+ ovaries in vitro, in order to clarify the role of FGF-10 and its relationship to other factors involved in ovarian development and function. Since the FGF-10 null mutation is neonatal lethal, ovaries from FGF-10 -/- mice will be recovered at birth and used in the following experimental approaches: (1) transplantation of FGF-10 -/- ovaries into normal ovariectomized female hosts, and (2) culture of neonatal ovaries in vitro. Analysis by histology, immunocytochemistry, RT-PCR, and in situ hybridization will yield valuable information about ovarian development and function.